Performance of amide proton transfer imaging to differentiate true progression from therapy-related changes in gliomas and metastases

Abstract Objectives Differentiating true progression or recurrence (TP/TR) from therapy-related changes (TRC) is complex in brain tumours. Amide proton transfer-weighted (APT) imaging is a chemical exchange saturation transfer (CEST) MRI technique that may improve diagnostic accuracy during radiological follow-up. This systematic review and meta-analysis elucidated the level of evidence and details of state-of-the-art imaging for APT-CEST in glioma and brain metastasis surveillance. Methods PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for original articles about glioma and metastasis patients who received APT-CEST imaging for suspected TP/TR within 2 years after (chemo)radiotherapy completion. Modified Quality Assessment of Diagnostic Accuracy Studies-2 criteria were applied. A meta-analysis was performed to pool results and to compare subgroups. Results Fifteen studies were included for a narrative synthesis, twelve of which (500 patients) were deemed sufficiently homogeneous for a meta-analysis. Magnetisation transfer ratio asymmetry performed well in gliomas (sensitivity 0.88 0.82–0.92, specificity 0.84 0.72–0.91) but not in metastases (sensitivity 0.64 0.38–0.84, specificity 0.56 0.33–0.77). APT-CEST combined with conventional/advanced MRI rendered 0.92 0.86–0.96 and 0.88 0.72–0.95 in gliomas. Tumour type, TR prevalence, sex, and acquisition protocol were sources of significant inter-study heterogeneity in sensitivity ( I 2 = 62.25%; p < 0.01) and specificity ( I 2 = 66.31%; p < 0.001). Conclusion A growing body of literature suggests that APT-CEST is a promising technique for improving the discrimination of TP/TR from TRC in gliomas, with limited data on metastases. Clinical relevance statement This meta-analysis identified a utility for APT-CEST imaging regarding the non-invasive discrimination of brain tumour progression from therapy-related changes, providing a critical evaluation of sequence parameters and cut-off values, which can be used to improve response assessment and patient outcome. Key Points Therapy-related changes mimicking progression complicate brain tumour treatment . Amide proton imaging improves the non-invasive discrimination of glioma progression from therapy-related changes . Magnetisation transfer ratio asymmetry measurement seems not to have added value in brain metastases .